The aim of this study was to evaluate the prognostic impact of anemia in outpatients with chronic heart failure attending specialized heart failure clinics and specifically to investigate its prognostic utility in patients with severe renal dysfunction or advanced heart failure.
Anemia is an independent prognostic marker in patients with heart failure. The effect of anemia on mortality decreases with increasing creatinine levels.
Multivariate Cox regression analyses were used to investigate the prognostic effect of anemia in 4,144 patients with heart failure from 21 outpatient heart failure clinics in Norway. Severe renal failure was defined as estimated glomerular filtration rate =45 ml/min/1.73 m(2) and advanced heart failure as New York Heart Association functional classes IIIb and IV.
Baseline anemia was present in 24% and was a strong predictor of all-cause mortality (adjusted hazard ratio [HR]: 1.30, 95% CI: 1.09 to 1.56, p = 0.004). Baseline anemia did not predict mortality in the 752 patients with severe renal dysfunction (adjusted HR: 1.08, 95 % CI: 0.77 to 1.51, p = 0.662) and the 528 patients with advanced heart failure (adjusted HR: 0.87, 95% CI: 0.56 to 1.34, p = 0.542). In the 1,743 patients who attended subsequent visits, sustained anemia independently predicted worse prognosis (adjusted HR: 1.47, 95% CI: 1.10 to 1.94, p = 0.008), whereas transient and new-onset anemia did not.
According to our study, baseline anemia was not an independent predictor of all-cause mortality in outpatients with heart failure and accompanied severe renal dysfunction or advanced heart disease. Sustained anemia after optimizing heart failure treatment might imply worse prognosis independently of renal function and New York Heart Association functional class.
BACKGROUND: Dose requirements of epoetin vary considerably among patients with end-stage renal disease (ESRD), whereas determinants of epoetin sensitivity are poorly understood. Fat mass is an important source of adipokines, including interleukin 6 (IL-6), which is associated with decreased epoetin sensitivity. Furthermore, the adipokine leptin stimulates human erythroid development in vitro. In the present study, we investigate the impact of fat mass and leptin level on epoetin sensitivity in patients with ESRD. METHODS: One hundred sixty-six patients with ESRD (107 men; 64%) with a mean age of 56.9 +/- 0.9 years were studied in a post hoc cross-sectional analysis. Body composition was analyzed by dual-energy X-ray absorptiometry and correlated with serum markers of inflammation and leptin (analyzed by enzyme-linked immunosorbent assays), as well as with epoetin dose, in international units administered per week (IU/wk). To correct for differences in body mass and hemoglobin (Hb) levels, epoetin sensitivity was approximated as epoetin/Hb ratio, ie, epoetin dose per unit of Hb (IU/wk/g/dL) and epoetin/Hb/kg ratio, ie, epoetin dose per unit of Hb and kilogram of patient body weight (IU/wk/Hb/kg). RESULTS: Patients were divided into 3 groups according to epoetin/Hb/kg ratio (no-epoetin group, low-epoetin group, and high-epoetin group). The 3 groups had significantly different serum levels of high-sensitivity C-reactive protein (hsCRP; median, 8.6 versus 3.1 and 8.0 mg/L, respectively; P
Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted.
More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay.
Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies.
Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.
Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated.
A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm.
Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P
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Effect of cystatin C levels on angiographic atherosclerosis progression and events among postmenopausal women with angiographically decompensated coronary artery disease (from the Women's Angiographic Vitamin and Estrogen [WAVE] study).
End-stage renal disease and mild renal insufficiency are associated with increased cardiovascular risk. Cystatin C, a novel marker of kidney function, was found to be associated with a higher frequency of cardiovascular events and mortality independent of glomerular filtration rate. It remained uncertain, however, whether enhanced cardiovascular risk associated with cystatin C is due to accelerated progression of atherosclerosis or to plaque instability. The aim of this study was to examine the effects of baseline cystatin C on annual change in coronary artery narrowing and clinical events in 423 postmenopausal women with angiographically documented coronary artery disease enrolled in the Women's Angiographic Vitamin and Estrogen (WAVE) trial. Baseline and follow-up (mean 2.8 ± 0.9 years) angiography was performed in 320 women. Angiographic progression of disease and clinical events in each cystatin C quartile were compared. Women with cystatin C levels in the highest quartile were older and more likely to have histories of heart failure and stroke. Annualized changes in minimal and average luminal diameters were similar in diseased and nondiseased segments. All-cause death or myocardial infarction (3.6% vs 15.6%, p
The effects of different hemoglobin targets when using erythropoiesis-stimulating agents on quality of life are somewhat controversial, and predictors of change in quality of life in endstage renal disease have not been well characterized.
Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 weeks, using epoetin_alfa as primary therapy. Patients and attending physicians were masked to treatment assignment. Quality of life, a secondary outcome, was prospectively recorded using the Kidney Disease Quality of Life (KDQoL) questionnaire at weeks 0, 24, 36, 48, 60, 72, 84, and 96, with prespecified outcomes being fatigue and quality of social interaction.
The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr. Mortality was low, reflecting the relatively healthy group enrolled. Of 20 domains within the KDQoL only the prespecified domain of fatigue showed significant change over time between the two groups. Improvement in fatigue scores in the high-target group ranged from 3.2 to 7.9 over time (P = 0.007) compared with change in the low-target group. Higher body mass index and lower erythropoietin dose at baseline were independent predictors of improvement in multiple KDQoL domains.
In relatively healthy hemodialysis patients, normal hemoglobin targets may have beneficial effects on fatigue. Improvement in multiple domains of quality of life is associated with higher body mass index and lower erythropoietin requirements.
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Dialysis saves lives. However, dialysis alone cannot make those lives active and meaningful. Exercise, in particular, is critical in the rehabilitation of many individuals with chronic renal insufficiency The purpose of this pilot study was to: 1) examine changes in participants' physical capacity and quality of life with the intervention of a 12-week exercise program; 2) investigate whether erythropoietin (EPO) and antihypertensive medication dosages were reduced in the participants; 3) examine the feasibility of incorporating exercise into the London Health Sciences Centre (LHSC) hemodialysis program. A quasi-experimental one-group pre- and post-test design was utilized. Eight subjects completed the 12-week study. The exercise program involved a warm-up, stretching, strengthening, and cardiovascular training. The results demonstrated improvements in the participants'physical capacity, quality of life, and ability to perform activities of daily living (ADLs). There were no discernable trends in the participants' hemoglobin levels or EPO dosages. Although there were no statistically significant changes in participants' blood pressures, five out of the six participants who began the program on antihypertensive medications either had the dosages decreased or the drug(s) discontinued. Data from this small prospective study supports previous research that an exercise during dialysis program is safe and has the potential to result in positive patient outcomes.
BACKGROUND: Recent reports have indicated that icodextrin may interfere with glucose assays when patients are treated with icodextrin for peritoneal dialysis (PD). We wished to examine whether icodextrin interfered with plasma glucose, as measured with new instruments commonly used for glucose measurements in Norway. MATERIAL AND METHODS: Serum and plasma glucose were measured in a diabetic patient (type II) who had started PD with icodextrin. Serum glucose was measured simultaneously in venous blood using the laboratory reference method (hexokinase), and compared with eight point of care testing (POCT) glucometers. The instruments used glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ), glucose dehydrogenase nicotinamide adenine dinucleotide (GDH- NAD), or glucose oxidase (GOx) methods. RESULTS: The laboratory reference method for glucose measurements was not affected by icodextrin. Biosensors with GDH-NAD and GOx methods did not give falsely elevated glucose results. Two of the eight POCT glucometers used the GDH-PQQ method. Both Ascensia Contour (Bayer HealthCare) and Accu-Chek (Roche Diagnostics) showed more than 60 % higher glucose values than the reference method. INTERPRETATION: The GDH-PQQ method is non-specific for measurements of glucose. Over-estimation of glucose may result in unrecognized hypoglycaemia. POCT glucometers with a GDH-PQQ based monitoring system should not be used in diabetics receiving icodextrin for PD. The patients and caregivers must be informed about which glucometers to use.
Although left ventricular hypertrophy (LVH) is a characteristic finding in hemodialysis (HD) populations, few risk factors for progressive LVH have been identified.
As part of a multinational, blinded, randomized, controlled trial that demonstrated no effect of hemoglobin targets on LV size, 596 incident HD patients, without symptomatic cardiac disease or cardiac dilation, had baseline echocardiograms within 18 months of starting dialysis and subsequently at 24, 48, and 96 weeks later. A wide array of baseline risk factors were assessed, as were BP and hemoglobin levels during the trial.
The median age and duration of dialysis were 51.5 years and 9 months, respectively. LV mass index (LVMI) rose substantially during follow-up (114.2 g/m(2) at baseline, 121 at week 48, 123.4 at week 48, and 128.3 at week 96), as did fractional shortening, whereas LV volume (68.7, 70.1, 68.7, and 68.1 ml/m(2)) and E/A ratio remained unchanged. At baseline, the only multivariate associations of LVMI were gender and N terminal pro-B type natriuretic peptide. Comparing first and last echocardiograms in those without LVH at baseline, independent predictors of increase in LVMI were higher time-integrated systolic BP and cause of ESRD. An unadjusted association between baseline LVMI and subsequent cardiovascular events or death was eliminated by adjusting for age, diabetes, systolic BP, and N terminal pro-B type natriuretic peptide.
Progressive concentric LVH and hyperkinesis occur in HD patients, which is partly explained by hypertension but not by a wide array of potential risk factors, including anemia.
Cites: J Am Soc Nephrol. 2000 May;11(5):912-610770969